Cytomegalovirus (CMV) is an important opportunistic pathogen in transplant recipients, AIDS patients and pregnant women. Glycoprotein B (gB) is a protein found on the surface of CMV which contains the major neutralizing epitopes for this virus. A gB vaccine preparation has been shown to induce levels of neutralizing antibody comparable to those found in naturally infected individuals, but it is not known if such antibodies can protect against CMV infection. Transplant patients represent a unique population because they are challenged with CMV present in the donated organ or reactivated endogenously. We have followed substantial numbers of transplant patients in natural history studies to show that: 1) the quantity of CMV DNA detected by polymerase chain reaction, "CMV load" is the major determinant of CMV disease; 2) preexisting natural immunity can moderate the rate of increase of viral load; 3) CMV disease can be prevented by giving pre-emptive therapy before the viral load reaches high values. We now propose a 3-year study to immunize patients awaiting transplantation with CMV gB vaccine and determine if the antibodies induced can moderate the rate of increase of viral load seen post-transplantation. A total of 140 patients will receive CMV gB vaccination according to a placebo-controlled schedule giving single doses (20 mu/g as studied in normals), double doses and booster doses. Vaccine recipients will be followed to determine the durability of gB-vaccine-induced neutralizing antibody titers. Those patients (estimate 105) who proceed to transplant will be followed with serial measures of CMV load. The rate of increase in viral load will be compared for those who receive vaccine versus those allocated placebo. If a vaccine schedule can be identified which controls viral load, this will be recommended for a phase II placebo-controlled trial of clinical efficacy.